[Urothelial neoplasms in individuals younger than 20 years show very few genetic alterations and have a favourable clinical outcome].

Aims: Urothelial neoplasms in patients 19 years or younger are rare, with conflicting data regarding clinical outcome and no molecular data available.

Methods: Urothelial tumors of 14 patients 4 to 19 years old were identified, reclassified according to the 2004 WHO classification and data on presentation, risk factors and outcome were collected. 14 cases were microdissected and extensive molecular analyses were done, including FGFR3 and TP 53 mutation screening, Comparative Genomic Hybridisation (CGH), Urovysion FISH analysis, PCR for HPV, microsatellite analysis using an extended NIH consensus panel for detection of microsatellite instability (MSI) and 6 LOH markers on chromosome arms 17p, 9p and 9q and immunohistochemistry for TP 53, MIB1, CK20 and the mismatch repair proteins hMSH2, hMLH1 and hMSH6.

Results: Based on the 2004 WHO classification, 1 urothelial papilloma, 7 PUNLMPs, 5 low grade, and 1 high grade papillary urothelial cancers were included. There were no multifocal tumors and only 1 patient had recurrence. All patients were alive with no evidence of disease (4.5 years follow-up). We did not find mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss or HPV positivity. Chromosomal alterations in CGH, urothelial dedifferentiation with CK20 over-expression or aneuploidy were rare and only detected in 3 cases. One TP53 mutation was found in the only tumor with overexpression of TP53.

Conclusions: Urothelial neoplasms in individuals younger than 20 years have predominantly a low grade and favourable clinical outcome. The most frequent genetic alterations found in elderly patients are extremely rare. Urothelial neoplasms in young patients could represent a biologically distinct form of bladder disease with lack of genetic instability in most cases.